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Meal timing, fasting and glucocorticoids interplay in serum leptin ...

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184 A Elimam <strong>and</strong> C Marcus EUROPEAN JOURNAL OF ENDOCRINOLOGY (2002) 147<br />

Diagnostics, Mannheim, Germany). Serum <strong>in</strong>sul<strong>in</strong> <strong>and</strong><br />

cortisol concentrations were determ<strong>in</strong>ed by RIA with<br />

Pharmacia Insul<strong>in</strong> RIA (Pharmacia & Upjohn, Uppsala,<br />

Sweden) <strong>and</strong> DSL Cortisol RIA (Diagnostic Systems Laboratories,<br />

Webster, TX, USA) respectively.<br />

Statistics<br />

Data are presented as means^S.E., <strong>and</strong> statistical significance<br />

was accepted at P # 0:05: Statistical analysis<br />

was done on absolute values, while <strong>in</strong> the figures the<br />

data are presented as percent change from basel<strong>in</strong>e.<br />

Statistical differences over time were calculated by<br />

ANOVA for repeated measurements with post-hoc test<strong>in</strong>g<br />

us<strong>in</strong>g Tukey’s test where appropriate. The variables<br />

were log transformed for the analysis when they were<br />

not normally distributed. Data were analysed with the<br />

program Statistica (Statsoft, Inc., Tulsa, OK, USA).<br />

Results<br />

Serum lept<strong>in</strong> <strong>in</strong>creased significantly with<strong>in</strong> 5 h<br />

follow<strong>in</strong>g each meal (P , 0:01; Fig. 2). In the groups<br />

eat<strong>in</strong>g 12-hourly, lept<strong>in</strong> decl<strong>in</strong>ed <strong>in</strong> the even<strong>in</strong>g but<br />

rose aga<strong>in</strong> <strong>in</strong> response to the even<strong>in</strong>g meal. The rise<br />

<strong>in</strong> lept<strong>in</strong> after the meal taken <strong>in</strong> the even<strong>in</strong>g (36 h)<br />

was greater than after the same meal taken <strong>in</strong> the<br />

morn<strong>in</strong>g (P , 0:001; Figs 2 <strong>and</strong> 3). In those <strong>fast<strong>in</strong>g</strong><br />

for 48 h, lept<strong>in</strong> decreased by 60% <strong>and</strong> showed no diurnal<br />

variation. Lept<strong>in</strong> rise was higher follow<strong>in</strong>g 48 h of<br />

<strong>fast<strong>in</strong>g</strong> when compared with the response on day 1 <strong>in</strong><br />

the same <strong>in</strong>dividuals or the response to the same<br />

Lept<strong>in</strong> response to a st<strong>and</strong>ard meal<br />

(% change)<br />

www.eje.org<br />

60<br />

50<br />

40<br />

30<br />

20<br />

10<br />

0<br />

<strong>Meal</strong>s at 0, 24, 36 <strong>and</strong> 48 h<br />

<strong>Meal</strong>s at 0, 24, 36 <strong>and</strong> 48h (DEX)<br />

<strong>Meal</strong>s at 0 <strong>and</strong> 48h<br />

<strong>Meal</strong>s at 0 <strong>and</strong> 48h (DEX)<br />

meal on day 3 <strong>in</strong> the groups eat<strong>in</strong>g 12-hourly<br />

(P , 0:02; Fig. 3).<br />

DEX <strong>in</strong>creased lept<strong>in</strong> concentrations <strong>in</strong> those eat<strong>in</strong>g<br />

<strong>in</strong>termittently (P , 0:02; Fig. 2). The difference was<br />

statistically significant at 2000 h on day 2, i.e. after a<br />

total of 0.4 mg DEX. Thereafter, the differences between<br />

the two groups were constant, i.e. no cumulative effect.<br />

There was no difference <strong>in</strong> lept<strong>in</strong> between those tak<strong>in</strong>g<br />

DEX <strong>and</strong> controls <strong>in</strong> the groups <strong>fast<strong>in</strong>g</strong> for 48 h.<br />

Glucose <strong>and</strong> <strong>in</strong>sul<strong>in</strong> <strong>in</strong>creased significantly follow<strong>in</strong>g<br />

each meal (P , 0:001; Figs 4 <strong>and</strong> 5). In the groups<br />

<strong>fast<strong>in</strong>g</strong> for 48 h, the rise <strong>in</strong> glucose <strong>and</strong> <strong>in</strong>sul<strong>in</strong> <strong>in</strong><br />

response to the meal taken on day 3 was significantly<br />

higher when compared with the response on day 1<br />

ðP , 0:001Þ:<br />

The diurnal rhythm for cortisol was ma<strong>in</strong>ta<strong>in</strong>ed <strong>in</strong> all<br />

groups (Fig. 6). The groups tak<strong>in</strong>g DEX tended to have<br />

lower nadirs, but the difference was not statistically<br />

significant.<br />

Discussion<br />

<strong>Meal</strong> at 0 <strong>Meal</strong> at 24h <strong>Meal</strong> at 36h (night) <strong>Meal</strong> at 48h<br />

<strong>Meal</strong> <strong>tim<strong>in</strong>g</strong><br />

We <strong>in</strong>vestigated the effect of different durations of<br />

<strong>fast<strong>in</strong>g</strong> with <strong>and</strong> without a low dose of <strong>glucocorticoids</strong><br />

on the lept<strong>in</strong> diurnal variation <strong>and</strong> response to a st<strong>and</strong>ard<br />

meal. In a previous study, we reported for the first<br />

time a 4-fold <strong>in</strong>crease <strong>in</strong> <strong>serum</strong> lept<strong>in</strong> <strong>in</strong> response to<br />

energy <strong>in</strong>take, TPN, given after surgery <strong>in</strong> otherwise<br />

healthy patients (28). In addition, we also reported<br />

that lept<strong>in</strong> concentrations did not decrease <strong>in</strong> response<br />

to <strong>fast<strong>in</strong>g</strong> <strong>in</strong> the control group that had only sal<strong>in</strong>e<br />

<strong>in</strong>fusion for 24 h after the surgery (28). Our hypothesis<br />

Figure 3 Mean^S.E. <strong>serum</strong> lept<strong>in</strong> response<br />

to a st<strong>and</strong>ard meal given at 0, 24, 36 <strong>and</strong><br />

48 h. The lept<strong>in</strong> response was calculated by<br />

subtract<strong>in</strong>g <strong>in</strong>dividual lept<strong>in</strong> levels just before<br />

eat<strong>in</strong>g a st<strong>and</strong>ard meal from the levels 5 h<br />

after the meal.

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